JPH0323865A - Medical material preparation thereof and medical appliance using the same material - Google Patents

Abstract

PURPOSE:To obtain a medical material showing excellent bio-compatibility stable over a long period of time by forming the medical material from a high-molecular compound, a copolymer, fatty acid and a fatty acid macromer and bonding the copolymer to the high-molecular compound through a covalent bond and bonding fatty acid and the fatty acid macromer to the copolymer through a covalent bond. CONSTITUTION:The first process bonding fatty acid, the functional group of a fatty acid macromer and a part of the functional group of a copolymer through a covalent bond and the second process bonding a part of the functional group of the copolymer to the functional group of a high-molecular compound through a covalent bond are provided. A part of the functional group of the copolymer in the first process is pref. a carboxyl group and a part of the functional group of the copolymer in the second process is pref. an epoxy group. Further, at least the part brought into contact with blood consists of the high-molecular compound, the copolymer, fatty acid or/and the fatty acid macromer and the copolymer is bonded to the high-molecular compound by a covalent bond. A medical appliance formed by containing a medical material wherein fatty acid and the fatty acid macromer are bonded to the copolymer through the covalent bond is provided.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to medical materials, methods for producing the same, and medical instruments.

Conventional technology> Medical devices such as artificial organs that have parts that come into contact with blood have been manufactured and used in the past, but when selecting the materials that make up these medical devices, it is important to consider biocompatibility. is an important issue. This biocompatibility is an important factor depending on the surface quality of the medical device used. On the other hand, it goes without saying that physical properties as a medical device are also important.

Therefore, it is considered effective to select a material with appropriate physical properties for a medical device and modify its surface properties when applied as a medical material. fact,
From this point of view, various surface modification methods have been proposed. One of them is a lipid-soluble vitamin or a fatty acid macromer having a reactive end, in which the reactive end is bonded to a base material (Japanese Patent Application Laid-Open No. 130069/1983).
Publication No., Terumo Corporation).

Problems to be Solved by the Invention> This was revolutionary in that it fully exhibited the physical properties of the base material as a medical material while imparting biocompatibility to its surface. It could not be said that sufficient biocompatibility was obtained, and there was room for improvement in improving biocompatibility.

Therefore, an object of the present invention is to provide a novel medical material, a method for manufacturing the same, and a medical device that solve the above-mentioned problems.

Another object of the present invention is to provide a medical material that stably exhibits excellent biocompatibility over a long period of time, a method for producing the same, and a medical device.

<Means for Solving the Problems> In order to achieve the above objects, as a result of intensive studies, the present invention comprises a polymer compound, a copolymer, and a fatty acid or/and a fatty acid macromer. Provided is a medical material comprising a copolymer covalently bonded and a fatty acid or/and a fatty acid macromer covalently bonded to the copolymer.

Furthermore, the present invention provides a first step of covalently bonding a functional group of a fatty acid or/and a fatty acid macromer to a functional group part of a copolymer, and a first step of covalently bonding a part of the functional group of the copolymer to a polymer compound. and a second step of covalently bonding the functional group of the medical material.

Further, in the present invention, some of the functional groups of the copolymer in the first step are carboxyl groups, and some of the functional groups of the copolymer in the second step are epoxy groups. preferable.

Further, the present invention provides that at least the part that comes into contact with blood is made of a polymer compound, a copolymer, and a fatty acid or/and a fatty acid macromer, and the copolymer is covalently bonded to the polymer compound, and the copolymer Provided is a medical device containing a medical material to which fatty acids and/or fatty acid macromers are covalently bonded.

The present invention will be explained in more detail below.

The medical material of the present invention consists of a polymer compound, a copolymer, and a fatty acid or/and a fatty acid macromer, in which the copolymer is covalently bonded to the polymer compound, and the copolymer has a fatty acid or/and a fatty acid macromer. It is characterized by covalently bonded macromers. In this way, in the medical material of the present invention, fatty acids and/or fatty acid macromers are covalently bonded to the polymer compound via the copolymer, so that a large number of fatty acids are fixed to one bonding point of the polymer compound. It has been shown to have superior biocompatibility, does not release fatty acids, and exhibits stable biocompatibility over a long period of time. In addition, if a fatty acid macromer is used, it is expected that the presence of a molecular chain (part of the spacer) between the fatty acid and the block copolymer will have an effect of suppressing platelet adhesion, so it will have higher biocompatibility. The molecular button length can also be easily controlled, and stable motility can be expected. In addition, the functional group of the copolymer consists of a functional group that binds to a fatty acid or/and a fatty acid macromer and a functional group that binds to a polymer compound, such as a functional group that binds to a fatty acid or/and a fatty acid macromer. If the functional group that binds to a carboxyl group or a polymer compound has an epoxy group, it is possible to easily adjust the amount of fatty acid or/and fatty acid macromer and polymer compound bound to the copolymer. .

Examples of the functional groups contained in the copolymer include epoxy groups, carpoxyl groups, and aldehyde groups. The raw material for the copolymer having an epoxy group is preferably (meth)acrylic acid-based glycicyl ester, and the raw material monomer for the copolymer having a carboxyl group is (meth)
Acrylic acid is preferred. In addition, in order to synthesize any silk-based polymer, esters such as (meth)acrylic acid esters, furthermore, medyl (meth)acrylate,
(meth)ethyl acrylate, (meth)probyl acrylate, (meth)isobrobyl acrylate, (meth)butyl acrylate, (meth)isobutyl acrylate, (meth)
Examples include 1-loxymethyl acrylate, 1-loxymethyl (meth)acrylate, and mixtures thereof.

When obtaining a copolymer using the above-mentioned monomers, a polymerization initiator such as ceric ammonium nitrate or ferrous hydrogen peroxide salt may be used.

The weight ratio of monomers having epoxy groups in the copolymer is 0
01% to 60% by weight, depending on your preference. If the weight ratio of the monomer having an epoxy group exceeds 60% by weight, it is not preferable because the polymer tends to become kelp during synthesis. Furthermore, it is possible to use one or more monomers having epoxy groups in the above copolymer, but in order to perform surface modification, 0.
0.01% by weight or more is preferable.

The molecular weight of the copolymer is preferably 500 to 500,000. When it is within this range, even if the number of bonding parts with the polymer compound is small, the surface treatment area of the copolymer is large, so that the effect of the copolymer can be sufficiently exhibited.

Specifically, when the molecular weight is less than 500, it is difficult to efficiently cover the entire surface of the material.
At higher molecular weights, the polymer's melt angle q property and reactivity with the surface of the material decreases, so the use of the polymer decreases with <<t.

In the present invention, among the large number of saturated fatty acids or unsaturated fatty acids that constitute the polymer derivative, the unsaturated fatty acids elisic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, and eiko saventaenoic acid, or the saturated fatty acid lauric acid,
Examples include myristic acid, bentacylic acid, valmitic acid, stearic acid, etc. Among them, linoleic acid is particularly preferred because it is particularly compatible with blood. In the present invention, each fatty acid may be used alone or as a mixture.

In the present invention, in order to improve blood compatibility,
These ligands are preferably bound as the fatty acid macromer via a spacer, preferably a hydrophilic spacer.

In addition, the term "macromer" generally refers to a polymer having a polymerizable functional group at the end, or in the specification, it refers to a polymer having a reactive functional group at the end in a broader sense. It should be interpreted as a thing.

Specific examples of the above-mentioned subedes include alkylene glycols having highly reactive functional groups at both ends r+rh, such as polyethylene glycol cyanide, polybrobylene glycol cyanide, and polytetramethylene glycol cyanide. preferable.

For example, when the spacer has an alkylene glycol skeleton, the degree of polymerization varies depending on the type of alkylene, or is preferably about 1 to 100. In particular, the alkylene glycol is polyethylene glycol. Polyethylene glycols having a degree of polymerization of 20 to 90 and polybrobylene glycols having a degree of polymerization of 10 to 50 are particularly preferred.

In the present invention, the copolymer having an epoxy group and the fatty acid or/and the fatty acid macromer undergo a graft copolymerization reaction via the epoxy group of the copolymer, or the epoxy group and the carboxyl group undergo a graft copolymerization reaction. The copolymer and the fatty acid macromer are graft copolymerized via the carboxyl groups of the copolymer to obtain a polymer derivative.

The above reaction may be a general synthetic reaction. On the other hand, as the polymer compound, cellulose and its derivatives are most preferably used, and in addition, polyvinyl alcohol, partially saponified polyvinyl acetate, ethylene vinyl alcohol copolymer, partially saponified ethylene vinyl acetate copolymer, etc. , polyacrylic acid or polymethacrylic acid and their copolymers, polyhydroxyethyl methacrylate, chitin, chitosan, collagen, polyacrylate, etc. can be used.

The reaction between a polymer derivative and a polymer compound is carried out by dissolving the polymer derivative in a suitable organic solvent such as acetone, methyl ethyl ketone, dioxane, tetrahydrofuran, etc., adding a Lewis acid catalyst and a basic catalyst, and then adding a polymer compound. This is done by adding .

Examples of the Lewis acid catalyst in the present invention include boron trifluoride, tin tetrachloride, and zinc chloride, with boron trifluoride being preferred from the viewpoint of reactivity.

In addition, as basic catalysts, among alkaline earth metals, hydroxides such as calcium, strontium, barium, radium, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, hydroxide, etc. Hydroxides of alkali metals such as francium are used, and among these, sodium hydroxide is most preferred from the viewpoint of solubility and reactivity.

The polymer compound referred to in the present invention includes various molded bodies, such as membranes,
A hollow system, a fiber, etc. can be used, and in that case, the reaction is carried out by immersing the molded body in a solution of a polymer derivative and a catalyst.

The reaction product thus obtained has biocompatibility. Furthermore, when a molded polymer compound is used, only the surface properties of the molded polymer compound can be changed without impairing the physical properties of the molded product, and the molded product can have biocompatibility. That is, the properties of the polymer compound that cause blood coagulation, activation of the immune system, deformation of platelets, etc. are reduced or eliminated, so it is particularly preferable to use it in areas that come into contact with blood.
For example, it is suitable as a material for artificial organs, dialyzers, blood filters, plasma separators, intravascular catheters, and the like.

Example Hereinafter, the present invention will be specifically explained based on Examples.

(Example 1) Synthesis of linoleic acid macromer Linoleic acid 2
00 g was dissolved in 70 mal of dry benzene, placed in a flask, and 14.8 g of phosphorus pentachloride was added in five portions under a nitrogen stream. After stirring at room temperature for 12 hours, the mixture was further refluxed for 2 hours. Next, benzene, phosphoryl trichloride, a reaction by-product, and hydrogen chloride were distilled off, and 14.0 g of linoleic acid chlorite was obtained by distillation under reduced pressure. (boiling point 15
5℃/1. 5 mml-1 g, yield 76%) 50.4 g of polyethylene glycol diamine (PGD-40 manufactured by Toray ■, molecular weight 4114) was placed in a flask. 1.48 g of triethylamine, and 120 g of dichloromethane
mI! ．． 3.66 g of linoleic acid chloride and 10% dichloromethane were added under a nitrogen stream and water-cooled (0°C).
The mfl solution was slowly added dropwise over 30 minutes. Thereafter, the mixture was stirred for 2 hours while gradually returning to room temperature.

After the reaction, triethylamine hydrochloride, a reaction by-product, was filtered off, triethylamine and dichloromethane were distilled off under reduced pressure, and the residue was dissolved in chloroform j00mA and diluted with water 1
Washed gently at 00 mil. The organic layer was separated, dried over anhydrous sodium sulfate, and then concentrated.
This was purified by flash chromatography using Wakogel C-300 (resolution solution: chloroform/methanol - 9/1 volume ratio) and 1 liter of purified product was obtained, yielding 137 g of purified product. (Yield 26%) The structure of this was confirmed using infrared spectroscopy (IR method) and proponent nuclear magnetic resonance method ('H-NMR method). It was confirmed that linoleic acid and PGD-40 were not contained in the m-U liquid THF). The results of the two characteristic values are shown below.

IR method/1550cm-'amitocarponyl stretching vibration 1
540cm-'Amit NH bending vibration 110[1cm-'x-TelCo stretching vibration'+1-11
MR method 6 0.9 ppm 6 1.3 ppm 6 3.7 ppm 6 5.3 ppm ? Nolic acid 1C. Unilinoleic acid -C ■Unipolyethylene glycol OCH2 C unilinoleic acid olefin C H = C H GPC method Retention capacity Purified product 11.4 mnPGD-
40 12.6m. C Linoleic acid 15 1 m (Example 2) In a synthetic glass polymerization tube for copolymer, 0.15 parts by weight of asohisisobutyronitrile and 7 5 parts by weight of methyl methacrylate were added as a polymerization initiator.
parts by weight, 15 parts by weight of glycidyl methacrylate,
6 parts by weight of 3-methacryloxybrobyltris(methoxy-1-xy)silane (Disso■), 1 5 parts by weight of methacrylic acid
parts by weight were charged, the polymerization tube was solidified by solidification in liquid nitrogen, and after repeated degassing in a vacuum bomb, nitrogen substitution, and degassing, the tube was sealed. This was heated in a constant temperature bath at a predetermined temperature for a predetermined time. After that, cool it down, open it, and pour the contents into a container.
A white polymer was obtained by dissolving it in lahydrofuran and reconcentrating it in methanol.

Similarly, a copolymer containing no methacrylic acid was synthesized.

Epoxy equivalents were determined by dissolving these copolymers in methyl ethyl chlorine and titrating with 0.0 IN perchloric acid/acetic acid solution using ethyltrimethylammonium bromide as a catalyst and crystal hydroxide as an indicator. was determined, and the glycicyl methacrylate composition was determined (Table 1).

Table 1 8 MM8/GMA/MPTMS/MA-7
．． 5/15/6/1.5 (weight 1 [ratio) B: MM8/GM8/MPTMS - 7.571577.5
(Gravity i ratio) MM 8-medinole methacrylate GMA: glycidyl methacrylate MPTMS: 3-methacryloxypropyltris (
(Metal xyel 1 xy) silane MA, methacrylic acid 16 (Example 3) Reaction of linoleic acid macromer and copolymer Copolymer No. obtained in Example 2. 4 of l. OOg, 0.718 g of dicyclohexylcarpodiimide and 100 mA of a mixed solvent of tetrawarmed carbon/acetonitrile (1:1 volume ratio) were placed in a flask, and the mixture was heated at room temperature for 60 minutes under a nitrogen stream.
After stirring for 12 minutes, 12 minutes of linoleic acid macromer of Example 1 was prepared.
．． A 20 mu solution of 0 g of carbon tetrachloride/1.Lyl acetonitrile (1:1 volume ratio) was gradually added to the mixture, and the mixture was stirred at room temperature for 60 minutes, and then further stirred at 60° C. for 60 minutes. After the reaction contents were allowed to warm to room temperature, the contents were filtered through a glass filter, and the solvent of the filtrate was lightly distilled off to obtain a yellow, highly viscous crude product.

200 mft of methanol was added to the obtained crude product, and the mixture was stirred at room temperature for about 30 minutes until there were no lumps left, followed by centrifugation, and the supernatant was removed by decantation. After performing the same operation twice more, vacuum drying was performed, and 9.63 g of polymer derivative (2) was obtained.

(Example 4) Reaction of linoleic acid macromer and copolymer Copolymer No. 2 obtained in Example 2. 2, 10.0 g of the linoleic acid macromer obtained in Example 1. and 80 mu of a benzene/THF (4:3 volume ratio) mixed solvent were placed in a flask and refluxed for 3 hours under a nitrogen atmosphere. After the reaction contents were cooled to room temperature, the solvent was lightly distilled off to obtain a yellow, highly viscous crude product. 100 mJ2 of methanol was added to the obtained crude product, and the mixture was stirred at room temperature for about 30 minutes until there were no lumps, followed by centrifugation, and the supernatant was removed by decantation. After performing the same operation two more times, vacuum drying was performed.
8.71 g of polymer derivative II was obtained.

(Example 5) Reaction of linoleic acid and copolymer with pyridine 0.
0.04 g of dry dioxane was added to 30 m<0>C, and then 0.90 g of linoleic acid was put into a flask using this mixture, and the mixture was stirred at 80<0>C for 30 minutes under a nitrogen stream. Furthermore, copolymer No. obtained in Example 2 was added to this flask. 2 of 3. O
After adding a solution of Og dissolved in 70 mA of dry dioxane and stirring at 80°C for 6 hours, the reaction contents were cooled to room temperature and the solvent was lightly distilled off, yielding a pale brown highly viscous crude product. It was done. 1 methanol to this crude product
After adding 00 mjl and stirring at room temperature for about 30 minutes (until there are no lumps), centrifugation was performed, and the supernatant was removed by decantation.

After performing the same operation twice more, vacuum drying was performed, and 305 g of polymer derivative IH was obtained.

(Example 6) Graft copolymerization of polymer derivatives onto regenerated cellulose membrane The polymer derivatives ①, II. II+ was graft copolymerized as follows.

Regenerated cellulose membrane (
0.3 g (film thickness: 0.2 mm) was immersed for 30 minutes. Next, 0.5 (
The cellulose membrane was immersed in an acetone solution of W/V)% and reacted at room temperature for 24 hours.

After the reaction is complete, take out the cellulose membrane, wash it thoroughly in the order of acetone, ethanol, and distilled water to prepare medical materials 1 and 1.
I, II+ and used as samples for the following examples.

(Example 7 and Comparative Example 1) Using the medical materials I, I+, and ■■ obtained in Example 6, the following evaluation tests 1 and 2 were conducted, and the results are shown in Tables 1 and 2. are shown respectively.

Evaluation test 1 Platelet diastolic ability test 3.8% sodium citrate (1/10 of the amount of blood collected)
Venous blood from a healthy individual was collected using a polypropylene syringe containing 800 r.p. p. Centrifuge for 5 minutes at
A platelet suspension was prepared. The platelet count of this platelet suspension was 66,000/mm'.

This platelet suspension is 0.2mf! ．． The polymer derivative-treated regenerated cellulose membrane samples (lcm2) obtained as medical materials I, II, and II+ in Example 6 and the untreated regenerated cellulose membrane sample (lcm2) as Comparative Example 1 were used.
m2) to a thickness of 2 mm, and were brought into contact for 30 minutes at room temperature. After a predetermined period of time, each sample was subjected to 3.
Wash lightly with 8% sodium citrate diluted solution, then 2
．． The sample was fixed in 5% glutaraldehyde/lactated Ringer's solution by storing it in a cool place overnight. An additional 3.8%
After washing lightly with a diluted sodium citrate solution, it was dehydrated in a series of ethanol (50%, 60%, 70%, 80%,
90%, 95%, 100%, and 100% ethanol solutions were treated in sequence for 10 minutes overnight. ), air dry,
Observation was made using a scanning electron microscope (JSM840 manufactured by JEOL Ltd.). The evaluation was based on the number of platelets attached to 0.07 mm2 and changes in their morphology. Morphological changes were classified into the following three types.

■Type. Platelets change from the normal disk shape to a spherical shape.
4. This is a piece of wood with pseudopods, which is thought to have relatively weak adhesion to the material surface.

++ type: A type with several or more pseudopodia extended and the cytoplasm extending to half of the pseudopod, which appears to have strongly adhered to the material surface.

Type III: A type with a thin cytoplasm that is more than half the length of the pseudopod, and the cytoplasm has expanded almost completely, exhibiting a cylindrical shape, and appears to have completely adhered to the material surface.

The test results are shown in Table 2.

Table 2 Evaluation test 2 Measurement of changes in complement value Medical use of the present invention obtained in Example 6, 14 II T,
＋＋． Regarding rivers, changes in compensation value were measured using the Mayer method shown below.

Each sample is pre-soaked in physiological saline and brought to a state of defeat equilibrium. Gently remove moisture from the surface of each sample, and
2, place it in a plastic test tube and add 1 mfL of adult dog serum. After activation by holding at 37° C. for 3 hours, the change in complement value CH50 (complement value by 50% hemolysis method) was measured and the consumption rate was calculated. The results are shown in Table 3.

Table 3 It is clear from Table 3 that the cellulose sheets of the present invention show a very small decrease in complement value CH502 4 in serum compared to untreated cells.

(Example 8 and Comparative Example 2) A cuprammonium regenerated cellulose hollow system was placed in a glass tube,
Connect one end to the aspirator and the other end to N a O H
O. It was immersed in a 5 (W/V)% aqueous solution. Furthermore, the hollow fibers were filled with an aqueous NaOH solution using the suction force of the asvilator.

After filling, the container was left at room temperature for 30 minutes. NaoH*m in the hollow fiber? After draining the water, the medical material obtained in Example 6 was filled with a 05 (W/V)% dioxane solution into a dialyzer using the same method, and the dialyzer was heated at room temperature for 2 hours.
It was left for 4 hours. Thereafter, the treated solution was discharged and washed with sioxane, and then thoroughly washed with acid and distilled water, and dried with air at a temperature of 25°C. Furthermore, in order to ensure complete drying, it was left in an oven at 60° C. overnight.

FIG. 1 shows a module for extracorporeal circulation experiments of the Tiarizer, and will be specifically explained.

That is, the dialyzer 1 forms a hollow fiber bundle 2 using copper ammonia regenerated cellulose hollow fiber 341 wood having an inner diameter of about 200 μm, an outer diameter of about 224 μm, and an effective length of 14 cm.
It was inserted into a cylindrical wooden body 3, and both ends were fixed with polyurethane bottling agents 4 and 5. Furthermore, headers 6 and 7 were attached to both ends and fixed with caps 8 and 9, thereby producing a dialyzer (artificial kidney) 1. .

The internal area of this membrane was 3000 m2.

In the dialyzer shown in FIG. 1, an inlet pipe 10 and an outlet pipe 11 for dialysate are provided near both ends of the cylindrical wooden body 3.

Thereafter, distilled water was filled, and the dialyzer in this state was placed in an autoclave and sterilized at a temperature of 115° C. for 30 minutes. Using this dialyzer, the following evaluation tests were conducted.

Evaluation test 3 Extracorporeal circulation test The rabbit was fixed in the dorsal position on a Kitajima fixation table.

Next, the hair in the surgical field was trimmed with electric clippers and wiped with alcohol cotton. An incision was made along the midline from the submandible to the clavicle with scissors, and the right (left) common carotid artery was removed, being careful not to open the fascia and damage the nerves, branch vessels, and surrounding tissues. Then, the left (right) facial vein was similarly carefully dissected deeply, and Terumo Corporation's Surflow (registered trademark of Terumo Corporation a!! ) An indwelling catheter was inserted and ligated and fixed. Similarly, a catheter was also inserted into the artery and ligated and fixed.

An experimental circuit was prepared for Rabbit 20 thus prepared using the dialyzer and, as a comparison, an untreated cuprammonium regenerated cellulose hollow fiber membrane dialyzer (Comparative Example 2) having a similar membrane area. That is, as shown in FIG. 2, the catheter 21 connected to the artery of the rabbit 20 was connected to the pump 22, and the chamber 23 and the vein of the rabbit 20 were connected through the catheter 25. The bomb 22 and the dialyzer 1 are connected by a tube 26, and the tube 26 is connected to the inlet 27 of the manometer.
It is connected to the side 27. Furthermore, the chamber 23 that communicates with the dialyzer 1 and the out 24 side of the manometer is connected to the tube 2.
Connected at 8. On the other hand, the dialysate inlet and outlet of the dialyzer 1 were connected by a tube 29, and a bomb 30 was installed in the tube 29, and the dialyzer 1 was immersed in a water bath 31 at 37°C. The circuit configured in this way has an IIU/m
Priming washing was performed with J2 heparinized saline (100ml).

Extracorporeal circulation was performed with the blood flow rate set at 10 mu'/min. No anticoagulant was used in the experimental conditions. Immediately after the start of circulation, 5 minutes, 10 minutes, 15 minutes, 20 minutes,
1 mJZ blood was collected after 30, 45, 60, and 120 minutes, and the collected blood was anticoagulated with 1.5% EDTA-2Na physiological saline, and then EL↑-8 (OrthIn
The number of blood cells was calculated using the following method (manufactured by Strument Inc.).

The white blood cell count (WBC) obtained as a result. Platelet count (P
LT) and hematocrit values (HCT) are shown in Tables 4 to 5. Table 4 shows data from an experimental circuit using the treated cuprammonium regenerated cellulose hollow fiber membrane dialyzer for medical material I obtained in Example 6, and Table 5 shows untreated cuprammonium as a control. Data from an experimental circuit using a regenerated cellulose hollow fiber membrane dialyzer (Comparative Example 2). The white blood cell count and platelet count were corrected for the Ht value using the following formula and expressed as the Ht value immediately before the start of circulation.

Cx: Correction value CO. Actual calculated value Htx: Correction reference It value = Initial Ht value Hto: Ht value when the Co value was obtained.Furthermore, fluctuations in the number of white blood cells based on these data are shown in a graph in FIG.

Table 4 Table 5 31 32 <Effects of the Invention> The medical material of the present invention has a fatty acid and/or a fatty acid macromer covalently bonded to a polymer compound via a copolymer. The blood coagulability of the polymer is reduced, activation of the complement system is suppressed, and platelet adhesion is suppressed, so that stable biocompatibility is imparted to the polymer compound over a long period of time. Further, according to the method for manufacturing medical materials of the invention, the above-mentioned medical materials can be manufactured extremely efficiently.

[Brief explanation of drawings]

FIG. 1 is a cutaway perspective view of a mosule for extracorporeal circulation experiments of a dialyzer applied to an embodiment of the present invention. FIG. 2 shows an experimental circuit used in an example of the present invention. FIG. 3 is a graph showing the results of temporal changes in white blood cells conducted in an example of the present invention. Explanation of symbols 1... dialyzer, 2... hollow fiber bundle, 3...
...Tubular wood body, 4, 5... Botting material, 6, 7... Header, 8, 9... Cap,
10...Artificial pipe, 11...Outlet pipe, 20.
・・Rabbit, 21・Catheter, 22・
...Bongbu, 23...Jangha 24...
Manometer out, 25... Catheter, 26... Tube, 2
7... Manometer in, 28... tube, 29.
...Tube, 30...Bomb, 3 1
··· water ? valley

Claims (4)

[Claims] (1) High molecular compound, copolymer, and fatty acid or/
and a fatty acid macromer, wherein a copolymer is covalently bonded to a polymer compound, and a fatty acid or/and a fatty acid macromer are covalently bonded to the copolymer. (2) In producing the medical material according to claim 1, a first step of covalently bonding a functional group of a fatty acid or/and a fatty acid macromer with a part of a functional group of a copolymer; 1. A method for producing a medical material, comprising a second step of covalently bonding a part of the functional group of the polymer compound to a functional group of the polymer compound. (3) A part of the functional groups of the copolymer in the first step are carboxyl groups, and a part of the functional groups of the copolymer in the second step are epoxy groups. A method for manufacturing the medical material described. (4) A medical device in which at least a portion that comes into contact with blood contains the medical material according to claim 1.